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Title: Structural Organization of a Full-Length Gp130/LIF-R Cytokine Receptor Transmembrane Complex

Abstract

gp130 is a shared receptor for at least nine cytokines, and can signal either as a homodimer, or as a heterodimer with Leukemia Inhibitory Factor Receptor (LIF-R). Here we biophysically and structurally characterize the full-length, transmembrane form of a quaternary cytokine receptor complex consisting of gp130, LIF-R, the cytokine Ciliary Neurotrophic Factor (CNTF), and its alpha receptor (CNTF-R{alpha}). Thermodynamic analysis indicates that, unlike the cooperative assembly of the symmetric gp130/Interleukin-6/IL-6R{alpha} hexameric complex, CNTF/CNTF-R{alpha} heterodimerizes gp130 and LIF-R via non-cooperative energetics to form an asymmetric 1:1:1:1 complex. Single particle electron microscopic (EM) analysis of the full-length gp130/LIF-R/CNTF-R{alpha}/CNTF quaternary complex elucidates an asymmetric structural arrangement, in which the receptor extracellular and transmembrane segments join as a continuous, rigid unit, poised to sensitively transduce ligand engagement to the membrane-proximal intracellular signaling regions. These studies also enumerate the organizing principles for assembly of the 'tall' class of gp130-family cytokine receptor complexes including LIF, IL-27, IL-12, and others.

Authors:
; ; ; ;
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
953567
Report Number(s):
SLAC-REPRINT-2009-316
Journal ID: ISSN 1097-2765; TRN: US201002%%1395
DOE Contract Number:  
AC02-76SF00515
Resource Type:
Journal Article
Journal Name:
Mol. Cell 31:737,2008
Additional Journal Information:
Journal Volume: 31; Journal Issue: 5; Journal ID: ISSN 1097-2765
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; COMPLEXES; ELECTRONS; LEUKEMIA; LIGANDS; LYMPHOKINES; PARTICLES; RECEPTORS; SIGNALS; THERMODYNAMICS; Other,OTHER, BIO

Citation Formats

Skiniotis, G, Lupardus, P J, Martick, M, Walz, T, and Garcia, K C. Structural Organization of a Full-Length Gp130/LIF-R Cytokine Receptor Transmembrane Complex. United States: N. p., 2009. Web.
Skiniotis, G, Lupardus, P J, Martick, M, Walz, T, & Garcia, K C. Structural Organization of a Full-Length Gp130/LIF-R Cytokine Receptor Transmembrane Complex. United States.
Skiniotis, G, Lupardus, P J, Martick, M, Walz, T, and Garcia, K C. 2009. "Structural Organization of a Full-Length Gp130/LIF-R Cytokine Receptor Transmembrane Complex". United States.
@article{osti_953567,
title = {Structural Organization of a Full-Length Gp130/LIF-R Cytokine Receptor Transmembrane Complex},
author = {Skiniotis, G and Lupardus, P J and Martick, M and Walz, T and Garcia, K C},
abstractNote = {gp130 is a shared receptor for at least nine cytokines, and can signal either as a homodimer, or as a heterodimer with Leukemia Inhibitory Factor Receptor (LIF-R). Here we biophysically and structurally characterize the full-length, transmembrane form of a quaternary cytokine receptor complex consisting of gp130, LIF-R, the cytokine Ciliary Neurotrophic Factor (CNTF), and its alpha receptor (CNTF-R{alpha}). Thermodynamic analysis indicates that, unlike the cooperative assembly of the symmetric gp130/Interleukin-6/IL-6R{alpha} hexameric complex, CNTF/CNTF-R{alpha} heterodimerizes gp130 and LIF-R via non-cooperative energetics to form an asymmetric 1:1:1:1 complex. Single particle electron microscopic (EM) analysis of the full-length gp130/LIF-R/CNTF-R{alpha}/CNTF quaternary complex elucidates an asymmetric structural arrangement, in which the receptor extracellular and transmembrane segments join as a continuous, rigid unit, poised to sensitively transduce ligand engagement to the membrane-proximal intracellular signaling regions. These studies also enumerate the organizing principles for assembly of the 'tall' class of gp130-family cytokine receptor complexes including LIF, IL-27, IL-12, and others.},
doi = {},
url = {https://www.osti.gov/biblio/953567}, journal = {Mol. Cell 31:737,2008},
issn = {1097-2765},
number = 5,
volume = 31,
place = {United States},
year = {Tue May 26 00:00:00 EDT 2009},
month = {Tue May 26 00:00:00 EDT 2009}
}